In vitro growth-inhibitory effects of quinoline compounds and their derivatives against intestinal bacteria associated with colorectal cancer

Štěpánka Rikanová

Master's thesis

Abstract:

Colorectal cancer (CRC) is one of the most common solid tumours of the colon or rectum. Recently the role of gut microbiome was observed to plays an important role in the development of CRC. Although no specific therapeutic measures have yet been established for the treatment of these pathogens in relation to the potential risk of CRC, chemotherapy based on conventional antibiotics of other agents (e.g. natural compounds) is being considered as a possible treatment. Current research is therefore focused on the discovery of new compounds, for example, derived from natural products. Quinolines are organic naturally occurring compounds in plants used in pharmacology and agriculture for their antimicrobial, anticancer and growth promoting properties. However, the effects of quinoline compounds on growth of bacteria association with CRC have not yet been investigated yet. In this study, six quinoline-based agents, namely carbadox, chloroxine, ferron, nitroxoline, oxyquinoline and olaquindox and six conventional antibiotics used to treat gastrointestinal diseases (ciprofloxacin, ceftriaxone, metronidazole, vancomycin, chloramphenicol, tetracycline) have been assayed for their in vitro growth-inhibitory effects against six pathogenic bacteria associate with CRC (Bacteroides fragilis, Clostridium septicum, Escherichia coli, Fusobacterium necrophorum, Peptostreptococcus anaerobius, Streptococcus bovis) using broth microdilution method. Antibacterial effect appeared to be strong for the fluoroquinoline antibiotic ciprofloxacin (MIC from 0.0625 to 2 μg/ml) and ceftriaxone (MIC from 0.025 to 32 μg/ml) from the cephalosporin group. The most effective quinoline compounds were the quinoxaline 1,4-dioxide carbadox (MIC ranging from 0.5 to 32 μg/ml) and the 8-hydroxyquinoline nitroxoline (MIC from 4 to 16 μg/ml), which were effective against all bacterial strains. These findings provide arguments for further investigation of quinoline compounds as prospective structures for modulation of gut microbiota composition in regard to suppressing of growth of bacteria associated with CRC.

Keywords

quinoline compounds, antimicrobial, MIC, broth microdilution method

Language used: English

Date on which the thesis was submitted / produced: 24. 4. 2023

Thesis defence

• Date of defence: 31. 5. 2023
• Supervisor: prof. Ing. Ladislav Kokoška, Ph.D.
• Reader: Lucie Malá, Ing.

Czech University of Life Sciences Prague

Faculty of Tropical AgriSciences

Master programme:
Tropical Forestry and Agroforestry